JAMIA MILLIA ISLAMIA

FACULTY OF LAW

Project on :

A Study on Drug Safety Monitoring Program in

India

SUBMITTED BY SUBMITTED TO
Aditya Pratap Singh
Mohd Aazam Mr. Subradipta
Sarkar
B.A.LL.B-8th semester
 ACKNOWLEDGEMENT

I would like to express my deepest and earnest gratitude to Mr. SUBRADIPTA SARKAR
faculty of Health Law, faculty of Law for giving me this opportunity to do a project on such a
valuable topic of A Study on Drug Safety Monitoring Program in India.

I am grateful for the assistance, guidance, and support that were extended during the course
of excellent research. I am also thankful to the college administration for providing the
resources necessary for thee research work. I thank my parents and friends their moral
support and love throughout my research work and Project preparation.

Above all I thank the God almighty for blessing me with the health and the vitality to
complete this project.

Aditya Pratap Singh

Mohd Aazam

B.A.LLB

8TH SEMESTER
 CERTIFICATE

I am glad to submit this project report on A Study on Drug Safety Monitoring Program in
India as a part of my academic assignment. The project is based on Research methodology
and further discusses the interview method.

I think this would be significant for academic purposes as well as prove Information to all the
readers.

Here though I declare that this paper is an original piece of research and the borrowed text
and ideas have been duly acknowledged.

Faculty Signature

________________
 DECLARATION

I, Aditya Pratap Singh, BA-LLB 8th Semester of Jamia Millia Islamia Universty do
hereby declare that this project is my original work and I have not copied this project or any
part thereof from any source without acknowledgement.

I am highly indebted to the authors of the books that I have referred in my project as well as
all the writers of all the articles and the owners of the information taken from the website for
it.

It is only because of their contribution and proper guidance of my faculty advisor Assist.
Prof. Mr. Supradipta Sarkar that I was able to gather light on the subject.

Aditya Pratap Singh

B.A.-LL.B

8th SEMESTER

I, Mohd Aazam, BA-LLB 8th Semester of Jamia Millia Islamia Universty do hereby
declare that this project is my original work and I have not copied this project or any part
thereof from any source without acknowledgement.

I am highly indebted to the authors of the books that I have referred in my project as well as
all the writers of all the articles and the owners of the information taken from the website for
it.

It is only because of their contribution and proper guidance of my faculty advisor Assist.
Prof. Mr. Supradipta Sarkar that I was able to gather light on the subject.

Mohd. Aazam

B.A.-LL.B

8th SEMESTER
 TABLE OF CONTENTS

 Abstract

 Pharmacovigilance in India, the need:

 National pharmacovigilance program of India

 Sub-committee to monitor banned drugs in India

 The role of pharmacist in drug safety

 Suggestions for improving ADR reporting

 Recommendations to improve drug safety in India

 Conclusions
Abstract
Pharmacovigilance is useful in assuring the safety of medicines and protecting the consumers
from their harmful effects. A number of single drugs as well as fixed dose combinations have
been banned from manufacturing, marketing and distribution in India. An important issue
about the availability of banned drugs over the counter in India is that sufficient adverse drug
reactions data about these drugs have not been reported. The most common categories of
drugs withdrawn in the last decade were nonsteroidal anti-inflammatory drugs (28%),
antidiabetics (14.28%), ant obesity (14.28%), antihistamines (14.28%), gastroprokinetic
drugs (7.14%), breast cancer and infertility drugs (7.14%), irritable bowel syndrome and
constipation drugs (7.14%) and antibiotics (7.14%). Drug withdrawals from market were
made mainly due to safety issues involving cardiovascular events (57.14%) and liver damage
(14.28%). Majority of drugs have been banned since 3-5 years in other countries but are still
available for sale in India. The present study compares the drug safety monitoring systems in
the developed countries such as the USA and UK and provides implications for developing a
system that can ensure the safety and efficacy of drugs in India. Absence of a gold standard
for a drug safety surveillance system, variations in culture and clinical practice across
countries makes it difficult for India to completely adopt another country's practices. There
should be a multidisciplinary approach towards drug safety that should be implemented
throughout the entire duration spanning from drug discovery to usage by consumers.
Adverse drug reactions (ADRs) are undesirable effects of medications that lead to large-scale
morbidity and mortality in developed countries.1 However, there is dearth of research that
claims ADR presence in developing countries such as India. A few studies have examined the
effects of ADRs mainly by looking at hospital readmissions2 Serious ADRs are seen in 6.7%
patients in India on an average and the number can be as high as 8% in rural South India 3 In
South India, ADRs are responsible for 0.7-3.4% hospital admissions, 3.7% hospital
readmissions and 1.3% mortality ADRs can be detected by yellow card reporting, a cost
effective method to monitor safe use of drugs. Yellow card reporting is useful in a number of
ways. It identifies unidentified ADRs, risk factors for the occurrence of ADRs, drug safety
issues and risk benefit comparisons among medications belonging to different therapeutic
classes.4 All the medications targeted for clinical purposes have to undergo several rigorous
preclinical and clinical testing as an evidence of their safety and effectiveness. At times,
adverse events are seen only upon usage among general population. The process whereby
adverse effects are detected through regular monitoring after the release of drug in market is
called pharmacovigilance.5

Drugs are often banned by the FDA or voluntarily withdrawn by the manufacturing
pharmaceutical company when the adverse events pose a risk greater than the benefit
provided by the drug. When drugs are used in combination with other drug(s) and if they
cause adverse events, then the drug(s) combination and not the individual drug are banned by
the FDA. Many drugs used as single dosage or in combination with other drugs are
discontinued from being produced and provided in the Indian market. 6 An extensive review
of the literature was done about the identified banned drugs for identifying the drug name
(generic and Brands), drug class, pharmacological category (use), manufacturer of the drug,

1
Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies.
Lazarou J, Pomeranz BH, Corey PN
JAMA. 1998 Apr 15; 279(15):1200-5.
2
Adverse drug reactions in a south Indian hospital--their severity and cost involved.
Ramesh M, Pandit J, Parthasarathi G
3
Ahmad A, Parimalakrishnan S, Mohanta GP, Manna PK, Manavalan R. Incidence of adverse drug reactions
with commonly prescribed drugs in tertiary care teaching hospital in India. Int J Pharm Sci. 2011;3:79–83
4
Spontaneous reporting of adverse drug reactions. I: the data.
Rawlins MD
Br J Clin Pharmacol. 1988 Jul; 26(1):1-5.
5
An evaluation of knowledge, attitude and practice of Indian pharmacists towards adverse drug reaction
reporting: A pilot study.
Ahmad A, Patel I, Balkrishnan R, Mohanta GP, Manna PK
Perspect Clin Res. 2013 Oct; 4(4):204-10.
6
Drugs banned in the Country. [Last accessed on 2012 Oct 5]. Available from:
http://www.cdsco.nic.in/writereaddata/drugs%20banned%20in%20thed%20country.pdf .
year of introduction in the Indian market, date of ban in India, the reason for ban and its
availability in India and in abroad. We also document the common category of drugs banned,
life span of the drug in the market. The search was conducted via databases such as PubMed,
Scopus and Sciencedirect (research articles, letter to the editor, editorials, commentaries) and
search engines such as Google and Google scholar (online news papers, and online providers
of health information and services to consumers, physicians, healthcare professionals).
Search terms indicating drug name (generic and brand name), pharmacotherapeutic use,
manufacturer's name, reason for withdrawal from the market, year of introduction and
withdrawal of the drug were used for researching individual drugs. The data was collected
using the Statistical Package for Social Sciences (SPSS) version 20.

Pharmacovigilance in India, the need:

According to the 2011 census, India has the second highest population in the world with over
1.21 billion people.7 The pharmaceutical industry in India is valued at 18 000 million dollars
and its growth is estimated at the rate of 12-14 % per annum. Pharmaceutical exports are also
growing at 25% compounded annual growth rate (CAGR) every year. The total export of
pharmaceutical products amounts to 8000 million dollars, which makes India a global
pharmacy of generic drugs since it is a distinct entity providing generic drugs, which have
quality and are affordable. On a global scale, India is being viewed as an emerging hub of
clinical trials, drug discovery, research and development. 8 After years of clinical trials and
step by step approval by drug regulatory authorities, a drug is introduced for curing a
particular disease. Prior to introduction in the market, despite several checks in the drug
discovery and development process, certain drugs are withdrawn from the market when
ADRs associated with them are discovered. Drugs might be withdrawn even after they are
available in the market for a decade or longer. Examples of such drugs are rosiglitazone,
rofecoxib, gatifloxacin, rimonabent and especially nimusulide formulation used in the market
since 12 years.9 Some of the ADRs are avoidable. Spontaneous reporting by healthcare
professionals is an important step for preventing or reducing ADR.10 The ADR reporting rate

7
Ahmad A, Parimalakrishnan S, Mohanta GP, Manna PK, Manavalan R. Incidence of adverse drug reactions
with commonly prescribed drugs in tertiary care teaching hospital in India. Int J Pharm Sci 2011;3:79-83.
8
Pharmacovigilance Programme of India for assuring drug safety. Available from:
http://www.cdsco.nic.in/pharmacovigilance.htm.
9
After ban in India, docs warn diabetics of rosiglitazone use. Available from:
http://www.indianexpress.com/news/after-ban-in-india-docs-warndiabetics- of-r/694755/
10
Sreeraman Sub-committee Formed to Check the Circulation of Banned Drugs in India. Available from:
http://www.medindia.net/ news/Sub-committee-Formed-to-Check-the-Circulation-of-Banned- Drugs-in-India-
25795-1.htm.
in India is below 1% compared to the worldwide rate of 5%. 11 Given the lower rate in India,
one of the reasons might be attributed to the awareness about pharmacovigilance and ADR
monitoring among the Indian healthcare providers.

National pharmacovigilance program of India

The national pharmacovigilance program (NPP) was established by the Ministry of Health
and Family Welfare in New Delhi in 2010 as a means to gather ADR reports throughout the
nation. The NPP comprises of a national coordinating center that receives ADR information
from individual pharmacovigilance centers about the cause, source and the personnel
involved in an adverse drug event via a vigiflow software interface operated by Uppsala
Monitoring Center.12 The NPP has developed and expanded through fives phases of
development since its initiation in 2010. In its initiation phase from 2010-2011, 40 medical
schools were established as pharmacovigilance centers and personnel were trained in these
pharmacovigilance centers. In the expansion and consolidation phase from 2011-2012,
additional 60 medical colleges were enrolled as part of NPP and gaps in training the
personnel working in the pharmacovigilance centers were identified. In the expansion and
maintenance phase from 2012-2013, another 100 medical colleges were enrolled as part of
NPP. In the expansion and optimization phase to be implemented in the future from 2013-
2014, the NPP plans to enroll an additional of 100 medical colleges. The NPP will also
establish the Centre of excellence for pharmacovigilance in Asia Pacific Region as part of the
excellence phase to be implemented in 2014-2015. Throughout the five phases, the NPP has
and will coordinate public awareness workshops for promoting drug safety and efficacy.

Sub-committee to monitor banned drugs in India

Each country has its own organization that monitors its individual circulation of banned
drugs. In India, prior to drug marketing, its safety and efficacy is ascertained in accordance
with the Schedule Y of Drugs and Cosmetics Act. Even after market approval, the safety and
efficacy of the drug is continuously examined on the basis of information gathered via
Pharmocovigilance, Post-Marketing Surveillance and information reported from other
countries. In order to examine such information, the Drugs Technical Advisory Board
(DTAB) under Drugs and Cosmetics Act has constituted a sub-committee, consisting of
11
Ahmad A, Patel I, Balkrishnan R, Mohanta GP, Manna PK. An evaluation of knowledge, attitude and practice
of Indian pharmacists towards adverse drug reaction reporting: A pilot study. Perspect Clin Res 2013;4:204-10.
12
Pharmacovigilance Programme of India for assuring drug safety. Available from:
http://www.cdsco.nic.in/pharmacovigilance.htm
experts on the subject who examine the information received from the sources mentioned
above and take a final view as to whether to prohibit the manufacture, sale and distribution of
drugs or to restrict its use and accordingly recommend the Government to make suitable
amendments under Section 26 A of the Drugs and Cosmetics Act which empowers the
Central Government to prohibit the manufacture, sale or distribution of such drug or
cosmetics.13

The role of pharmacist in drug safety

A multifaceted approach is required for safety of medicine regulation in the Indian market. A
useful first step is to establish transparency, which is not apparent presently. The pharmacist
can play a very important role in drug safety. Hence every state drug control officer should
strictly abide by the Drug and Cosmetic Act 1940, which mandates every pharmacy to have a
pharmacist at all times during business hours. Pharmacist can educate assistant pharmacists
as well as patients visiting the pharmacy by writing labels in easy and understandable
language, patient counseling, providing leaflets and stick posters about certain ADRs related
to the obtained medications and advice to report ADRs to pharmacists or other healthcare
professionals.

Continued education (CE) is very important for pharmacists for updating and refreshing their
knowledge about recent advancements and changes in pharmaceuticals. CE also helps in
educating pharmacists about the NPP including how to report and whom to report ADRs in
their practice. The government of India can also educate general population about black box
warnings via a media. Presently, only one Pharmacy College affiliated with the J.S.S.
Medical College and part of J.S.S. University, Mysore is involved in the NPP, but previously
even community pharmacies located in the state of Goa and many pharmacy colleges located
in south India acted as peripheral pharmacovigilance centers. Unfortunately, the NPP focuses
only on medical colleges and not on other healthcare facilities. Pharmacists and nurses are an
integral part of improving awareness about pharmacovigilance in India. Their efforts
contribute to the smooth running of the NPP and maintenance of up-to-date documentation
hence they should be given due recognition and considered an integral part of NPP.

The pharmacovigilance system in India is very poor and the increased workload on
physicians, nurses and pharmacists does not bring to their notice most of the ADRs occurring

13
Amrita P, Kharbanda B. Knowledge, Attitude and Skills of nurses of Delhi towards adverse drug reaction
reporting. Indian J Pharm Pract 2012;5:45-51.
in practice. Pharmacists are supposed to dispense accurate medications and they possess
prime knowledge on medications. Unfortunately in India the qualification for a pharmacist to
work in a pharmacy is a diploma (diploma in pharmacy a 2 year study plus 500 hour practical
training in hospital), and not a baccalaureate degree in pharmacy.

Moreover the educational curriculum in India for pharmacist is more focused on industry
rather than on community pharmacy. However, things are changing and courses based on
pharmacy practice are being taught in many pharmacy schools in South India as part of
programs such as Pharm. D. and M. Pharm. pharmacy practice. If the current generation of
pharmacists get involved in the NPP, we can expect an increase in the future detection of
ADRs being reported back to the concerned authorities, which in turn will help the
government to take the needed action at the earliest.14

Qualificatio Duratio Training Subjects related to Current

n n of needed for drug employment

registration as
  course pharmacist safety  

D.Pharm 2 year 500 hour in None Community

full time Hospital (3 Pharmacy/Hospital
months) pharmacy

B.Pharm 4 year One month in None Pharmaceutical

full time pharmaceutical industry/hospital

    industry   pharmacist,
community
pharmacy

Pharm.D. 5 year One year ADRs, Pharmacovigilance

full time Internship pharmacoepidemiology Industry, CROs,

      and drug safety Academia

Suggestions for improving ADR reporting

Electronic reporting of ADRs, inclusion of ADR education in the professional curriculum,
legal protection for healthcare professionals, information exchange about ADRs between
healthcare professionals, incorporating ADR information in patient charts, establishment of
pharmacovigilance centers at individual healthcare facilities, improving knowledge and
14
Srikanth BA, Ahmad A, Reddy KR, Balkrishnan R, Nagappa NA, Acceptance of doctor of pharmacy in India: A
survey based study, Arc Pharm Prac 2013;4:93-7.
awareness about ADR reporting among patients and healthcare professionals and better
coordination among pharmacovigilance centers at the local, state and the national levels are
some of the steps that can affect the mindset about ADR reporting in India.15

Recommendations to improve drug safety in India

Some recommendations to enhance drug safety in India include physicians prescribing
medications whose ADR profile is known, informing patients when new drugs are prescribed
and to be alert about possible ADRs, approval of new drugs with caution for diseases for
which safe alternatives are already existent, mention of drug approval date and black box
warnings on the label of medications, penalizing physicians and pharmacists involved in
prescribing or distribution of banned drugs, generation of awareness by the NPP about
banned drugs in the market and constituting a committee by the DTAB to regulate banned
drugs and medications with severe ADRs. The issue of circulation of banned drugs in the
Indian market is severe and public awareness about the safety concerns associated with using
banned drugs is imperative.

Conclusions
If all healthcare professional including physicians, nurses, pharmacist and others including
the patient report all ADRs then regulatory authority can take action as soon as possible, and
drugs which are banned worldwide may be not available in India too. The importance of
encouraging physicians, pharmacists, other health-care professionals, and patients to continue
to report serious suspected adverse drug reactions, whether unknown or known, to
manufacturers and their local regulatory agencies cannot be over emphasized. Drug
development is becoming increasingly difficult. Continued attrition of potentially useful
drugs because of serious unwanted effects will not help. Careful premarketing screening
should reduce the problem but may also reduce the number of potentially useful drugs
available for full development and subsequent licensing. Better risk management strategies
are needed to handle problems when they arise, by means other than revocation of licenses.

15
Ahmad A, Patel I, Balkrishnan R, Mohanta GP, Manna PK. An evaluation of knowledge, attitude and practice
of Indian pharmacists towards adverse drug reaction reporting: A pilot study. Perspect Clin Res 2013;4:204-10.